Could lipid antibodies unlock earlier Lyme diagnosis?

Clinical takeaway: Elevated anti-phosphatidic acid (αPA) and anti-phosphatidylserine (αPS) antibodies were detectable early in Lyme disease—including in many patients who remained seronegative by conventional testing—and persistent αPS elevation was associated with long-term post-treatment symptoms. These findings are promising but are not yet ready for clinical use.

Current Lyme disease tests often miss early infection and cannot determine whether symptoms reflect active, resolved, or post-treatment disease. Novel biomarkers that change with disease activity could improve diagnosis, monitoring, and future treatment strategies.

Investigators analyzed samples from approximately 200 individuals with acute or post-treatment Lyme disease and compared them with healthy controls and patients with conditions that can mimic post-treatment Lyme disease, including lupus, multiple sclerosis, fibromyalgia, long COVID, and chronic fatigue syndrome.

Three antiphospholipid antibodies were elevated during Lyme disease, with αPA and αPS standing out as potential markers of early infection. Among patients assessed at diagnosis, most had elevated αPA and αPS levels despite remaining negative on standard Lyme serology; roughly 75% of samples from one biobank cohort and nearly 70% from another were seronegative by conventional testing at enrollment.

Both antibodies rose early, peaked about 3 to 6 months after infection, and typically declined toward baseline after treatment. However, a subset of patients with post-treatment Lyme disease continued to show elevated αPS levels years after diagnosis, whereas αPA generally normalized. Persistent αPS elevation was largely absent in comparator autoimmune and chronic illness cohorts, suggesting a potentially distinct immune signature for some patients with prolonged Lyme-related symptoms.

“Persistent elevation in antiphosphatidylserine may drive autoimmune-like symptoms of Lyme disease in some patients and could serve as a biomarker for chronic disease,” the authors wrote.

The authors caution that larger prospective studies are needed to determine diagnostic accuracy and clinical utility before these markers can be incorporated into practice.

Source: Shrestha M, et al. (2026 June 30) Infect Immun. Antiphospholipid antibodies in acute and post-treatment Lyme disease